594 research outputs found
Demographic performance of local sheep and goat breeds in two agro-ecological zones in Egypt
Small breeders in Egypt raise locally adapted sheep and goats breeds, which have the ability to produce and reproduce under the prevailing harsh conditions. Improving resilience of their production system is a major challenge to support socioeconomic development. However, little is known about the productive abilities of these breeds in small farming systems. The present work is an attempt to assess the performance of local breeds in small farming systems, and their capacity to cope with feed scarcity and harsh climatic conditions. In 2018, a retrospective survey was conducted over 12 month period to assess demographic rates of 25 local Barki sheep and goat flocks in the rain-fed area of Coastal Zone of Western Desert (CZWD) and 28 local Saidi sheep and goat flocks under the hot intensive agriculture system in Upper Egypt (UE). Flocks are larger, reproductive performance and offtake rates are higher (and mortality lower) in the CZWD, a region specialized in small ruminant breeding whereas it remains a secondary activity in Upper Egypt. The marketing season is mainly during Korban Eid festival. Their main challenges are frequent incidence of drought in the CZWD and high prices of feed stuffs in both sites. Our study suggests breeders have different strategies in UE and the CZWD when confronted with feed shortage. Breeders in the CZWD purchase feed to maintain high herd productivity whereas in UE small ruminant breeding is a minor activity with less productive animals that are resilient to feed shortage
Exogenous WNT5A and WNT11 proteins rescue CITED2 dysfunction in mouse embryonic stem cells and zebrafish morphants
Mutations and inadequate methylation profiles of CITED2 are associated with human congenital heart disease (CHD). In mouse, Cited2 is necessary for embryogenesis, particularly for heart development, and its depletion in embryonic stem cells (ESC) impairs cardiac differentiation. We have now determined that Cited2 depletion in ESC affects the expression of transcription factors and cardiopoietic genes involved in early mesoderm and cardiac specification. Interestingly, the supplementation of the secretome prepared from ESC overexpressing CITED2, during the onset of differentiation, rescued the cardiogenic defects of Cited2-depleted ESC. In addition, we demonstrate that the proteins WNT5A and WNT11 held the potential for rescue. We also validated the zebrafish as a model to investigate cited2 function during development. Indeed, the microinjection of morpholinos targeting cited2 transcripts caused developmental defects recapitulating those of mice knockout models, including the increased propensity for cardiac defects and severe death rate. Importantly, the co-injection of anti-cited2 morpholinos with either CITED2 or WNT5A and WNT11 recombinant proteins corrected the developmental defects of Cited2-morphants. This study argues that defects caused by the dysfunction of Cited2 at early stages of development, including heart anomalies, may be remediable by supplementation of exogenous molecules, offering the opportunity to develop novel therapeutic strategies aiming to prevent CHD.Agência financiadora:
Fundação para a Ciência e a Tecnologia (FCT)
Comissão de Coordenação e Desenvolvimento Regional do Algarve (CCDR Algarve)
ALG-01-0145-FEDER-28044; DFG 568/17-2 Algarve Biomedical Center (ABC)
Municipio de Louléinfo:eu-repo/semantics/publishedVersio
SYNTHESIS, ANTITUMOR ACTIVITY, PHARMACOPHORE MODELING AND QSAR STUDIES OF NOVEL PYRAZOLES AND PYRAZOLO [1, 5-A] PYRIMIDINES AGAINST BREAST ADENOCARCINOMA MCF-7 CELL LINE
Objective: The present work aimed to synthesize New series of pyrazoles 3 and pyrazolo[1,5-a]pyrimidines 5, 7, 9 in order to evaluate their antiproliferative activity against human breast adenocarcinoma MCF-7cell line and study the cell cycle progression of the most active compounds. In addition, Pharmacophore modeling and QSAR Studies of these new compounds were done.Methods: The diazonium salt of 4-aminoacetophenone 1 was coupled with malononitrile in ethanol using sodium acetate affords 2-[(4-acetylphenyl)diazenyl] malononitrile Cycloaddition of hydrazine hydrate, in molar ratios 1:1 or 1:2, on compound 2, furnished 3,5-diaminopyrazolederivatives 3a and 3b respectively. Moreover, new pyrazolo[1,5-a]pyrimidine derivatives 5a-f were obtained upon cyclocondensation of 3a, b with different chalcones 4a-c in EtOH/piperidine,while compounds 7a-f were prepared via cycloaddition of 3a, b with various arylidene malononitriles 6a-c in the same reaction condition. Finally, treatment of 3a, b with ethyl 2-cyano-3-ethoxyacrylate 8a or 2-(ethoxymethylene)malononitrile 8b in EtOH/TEA yielded the novel pyrazolo[1,5-a]pyrimidine derivatives 9a, b respectively. These target compounds were screened for their cytotoxic activity against MCF-7 (human breast Cell Line) followed by study cell cycle of 7a. Finally, Pharmacophore modeling and QSAR Studies was carried out.Results: The pyrazolopyrimidine 7a was the most active compound (IC50 = 3.25 µM), whereas, some of the tested compounds exploited moderate growth inhibitory activity. Its effect was further studied on cell cycle progression; results showed that compound 7a induced cell cycle arrest at S-phase verifying this compound as a promising selective anticancer agent.Conclusion: Compound 7a was found to be the most active member against MCF-7 breast cancer (IC50= 3.25 μM), Further biological assessment of 7a using flow-cytometric analysis, revealed that it induced cell cycle arrest at S phase.Keywords: Pyrazole, Pyrazolo[1,5-a]pyrimidine, MCF-7 breast cancer cell line, Cell cycle profile, 3D pharmacophore,1 QSAR stud
Record of the first Pleonexes species (Crustacea: Amphipoda: Ampithoidae) in Moroccan waters: Pleonexes gammaroides Spence Bate, 1857
The ampithoid amphipod crustacean Pleonexes gammaroides Spence Bate, 1857 is reported from Morocco (northeastern Atlantic Ocean) for the first time, where it is the only representative of the genus Pleonexes Spence Bate, 1857 so far. Specimens were collected from the upper fringe of the infralittoral zone (including low intertidal) of El Jadida coastline associated with the holdfasts of the kelp Saccorhiza polyschides (Lightfoot) Batters (Phaeophyceae), colonising the sublittoral fringe in the southernmost distribution limit (Morocco). This finding updates the known geographical distribution of P. gammaroides in northern Africa and northeastern Atlantic. Some ecological and distributional details of this amphipod species are briefly discussed here.National Centre for Scientific and Technical Research (CNRST), Morocco 5UCD2017, AGA- KHAN Foundation under the project MARAFRICA AGA-KHAN/540316524/2019info:eu-repo/semantics/publishedVersio
Changes of Leptin concentration in plasma in patients with spinal cord injury: A Meta-analysis
Objective:The aim of this study was to investigate changes of leptin concentration in plasma in patients with spinal cord injury to come to a single concept by using a Meta-analysis.Setting:Systematic Review.Methods:Searching relevant articles was performed in Ovid data base, Medline (PubMed) EMBASE, Google Scholar, Cochrane and Scopus up to February 2013. Five articles were selected using two independent reviewers. Analysis were performed using SPSS version 18 and Comparative Meta-analysis software version 2.0.Results:The combined analysis with confidence interval of 95 using comprehensive meta-analysis showed significant higher leptin levels in patients with spinal cord injury in comparison with able bodies (P<0.0001). The effect of spinal lesion level on plasma leptin concentration was also statistically significant (P<0.0001). Body mass index was positively related to plasma leptin concentration in both groups (P<0.0001).Conclusion:This Meta analysis approves increased level of leptin in spinal cord injured patients which can be due to fat distribution changes and sympathetic dysfunction in these patients. Our results also showed that patients with higher spinal lesion level have higher plasma leptin concentration. © 2013 International Spinal Cord Society All rights reserved
Acoustic cell concentration, washing & perfusion for cellular therapy manufacturing
A major wave of promising cellular therapies is progressing through clinical trials, such that engineers and scientists need to address the challenges of economically ensuring the manufacture of safe and efficacious cell therapy products. These processes often depend on devices and methods that were developed for only related blood cell processing or vaccine manufacturing. Thus, we are in a window of opportunity to tailor innovative technologies to address the emerging specialized needs of cell therapy manufacturing. Concentrating and washing cells between stages is a repeated bioprocess unit operation, such as to transfer cells from culture medium to cryopreservation medium. Especially for small-scale autologous therapies, cell washing is not well performed by closed-system centrifuges or filters, including due to the loss of potentially lifesaving cells. We previously developed an acoustic cell separation device that has been widely used for 20 years as part of mammalian cell perfusion bioreactors. This non-fouling filter technology uses gentle ultrasonic standing wave forces to separate cells from medium based on density and compressibility differences. We have now adapted this technology to concentrate and then wash cells at high concentrations, so as to reduce the wash volumes by an order of magnitude, thereby reducing the process cost of goods compared to centrifuge washing. The device operation has been optimized to obtain greater than 99.9% washing with 95% washed cell recoveries, such that this acoustic technology could become the method of choice for cell therapy bioprocessing. We also have recently enhanced automated acoustic devices to perfuse over 140 million cell/mL cultures, maintaining \u3e99% cell separation efficiencies. With the simplicity of no physical filter barrier or mechanical moving parts, this tailored technology provides a high performance closed manufacturing device, to perfuse, concentrate and wash cells. The development of robust and economical means of mammalian cell manufacturing is on the critical path to ensuring that promising innovative therapies can become widely available to innumerable patients in dire need
Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study
Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world.
Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231.
Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001).
Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication
Mapping 123 million neonatal, infant and child deaths between 2000 and 2017
Since 2000, many countries have achieved considerable success in improving child survival, but localized progress remains unclear. To inform efforts towards United Nations Sustainable Development Goal 3.2—to end preventable child deaths by 2030—we need consistently estimated data at the subnational level regarding child mortality rates and trends. Here we quantified, for the period 2000–2017, the subnational variation in mortality rates and number of deaths of neonates, infants and children under 5 years of age within 99 low- and middle-income countries using a geostatistical survival model. We estimated that 32% of children under 5 in these countries lived in districts that had attained rates of 25 or fewer child deaths per 1,000 live births by 2017, and that 58% of child deaths between 2000 and 2017 in these countries could have been averted in the absence of geographical inequality. This study enables the identification of high-mortality clusters, patterns of progress and geographical inequalities to inform appropriate investments and implementations that will help to improve the health of all populations
Hydatid disease of the ribs: An exceptional location
Background. Hydatid disease is a zoonosis caused by larval stages of cestodes belonging to the genus Echinococcus. The rib location is exceptional. It presents a real diagnostic and therapeutic challenge.
Objective. To describe the clinical, serological and radiological features and surgical management of rib hydatidosis.
Methods. This is a retrospective study conducted over 4 years, on five cases of rib hydatidosis. We analysed the clinical and radiological presentations and the adopted therapeutic procedure.
Results. The average age of our patients was 44 years, without gender predominance. The clinical signs were dominated by the presence of an immobile swelling of fluid consistency without inflammatory sign, accompanied by moderate and intermittent localised pain. The laboratory assessment was nonspecific. The radiological assessment, including chest X-ray and thoracic computed tomography, with and without contrast, was essential in order to assess the extent of the lesion. Thoracic magnetic resonance imaging was requested in one case because of suspicions of a spinal extension. All of our patients underwent a rib excision accompanied by medical treatment of albendazole 24 hours after the surgery. The follow-up ranged from 1 year to 4 years and did not show any recurrence.
Conclusion. Hydatidosis of the ribs is an exceptional location of hydatid disease. The diagnosis was based on radiology and intraoperative exploration. The treatment remained essentially surgical by rib excision with anthelmintic drugs to prevent recurrence
Smart and Multi-Functional Magnetic Nanoparticles for Cancer Treatment Applications: Clinical Challenges and Future Prospects
Iron oxide nanoparticle (IONPs) have become a subject of interest in various biomedical fields due to their magnetism and biocompatibility. They can be utilized as heat mediators in magnetic hyperthermia (MHT) or as contrast media in magnetic resonance imaging (MRI), and ultrasound (US). In addition, their high drug-loading capacity enabled them to be therapeutic agent transporters for malignancy treatment. Hence, smartening them allows for an intelligent controlled drug release (CDR) and targeted drug delivery (TDD). Smart magnetic nanoparticles (SMNPs) can overcome the impediments faced by classical chemo-treatment strategies, since they can be navigated and release drug via external or internal stimuli. Recently, they have been synchronized with other modalities, e.g., MRI, MHT, US, and for dual/multimodal theranostic applications in a single platform. Herein, we provide an overview of the attributes of MNPs for cancer theranostic application, fabrication procedures, surface coatings, targeting approaches, and recent advancement of SMNPs. Even though MNPs feature numerous privileges over chemotherapy agents, obstacles remain in clinical usage. This review in particular covers the clinical predicaments faced by SMNPs and future research scopes in the field of SMNPs for cancer theranostics
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